Excessive alcohol consumption exerts damage on the liver, the primary site of ethanol metabolism. The balance between alcohol dehydrogenase and the catalases processing hydrogen peroxide means ethanol is normally converted to acetaldehyde and then acetate. Acetaldehyde is rapidly oxidised by mitochondrial acetaldehyde dehydrogenase (oxidative metabolism) to prevent toxicity.²⁰

However, excess alcohol can tip the enzyme balance towards reductive synthesis, meaning acetaldehyde is processed into fatty acids. In the early stages, fat deposits start to build in hepatocytes causing steatosis. This can occur over a long period of 4-5 drinks daily (around 14g ethanol per drink) or after a binge drinking session of 4-5 drinks in under two hours.

Steatosis is reversible if the person stops drinking alcohol, but continued alcohol consumption leads to a more severe type of inflammatory injury, steatohepatitis. Hepatocytes swell (‘ballooning degeneration’), there can be infiltration by neutrophils and there is a build-up of a matrix of proteins causing fibrosis. The later stages are widespread scarring and vascular changes, eventually causing liver failure.

Non-alcoholic fatty liver disease occurs through excess carbohydrate and fat consumption. Liver oxidation pathways are saturated so cannot convert the energy sources into carbon dioxide or export it as very low-density lipoproteins. Consequently, triglycerides accumulate in the liver. Foodstuffs particularly associated with this are fructose, sucrose, and high-fructose corn syrup, which can also stimulate lipid formation in hepatocytes, and saturated fat. Excessive levels of stored fatty acids in the liver also promote severe insulin resistance.²¹